Correlation and modulation of smooth muscle cells phenotypic switching induced by cytomegalovirus

Objective To explore the influence of murine cytomegalovirus on phenotypic modulation of vascular smooth muscle cell and modulation of PI3K/Akt pathway. Methods Male apoE knockout mice were injected abdominally with 2×105 PFU MCMV, followed by 16 weeks feeding. Then aortas were sectioned for HE staining and immunohistochemical staining of smooth muscle 22 alpha (SM22α) and osteopontin (OPN). Mouse aortic smooth muscle cells(MOVAS)were incubated with MCMV, then proliferation of MOVAS and expression of SM22a and OPN were tested. Western blotting test was applied to reveal MCMV’s modulation of PI3K/Akt pathway. Results The degree of atherosclerosis of apoE-/- mice in MCMV infection group was severe than that in control group, and OPN stain positive signals predominated in the arterial wall. After 24 hours of incubation with MCMV by 3×104 PFU, the expression of SM22a decreased (P=0.023), while OPN increased (P=0.034) in MOVAS. MCMV increased expression of Akt phosphorylation compared with the control group (P=0.035). The inhibitor of PI3K pathway LY294002 not only inhibited the phenotypic modulation of smooth muscle by MCMV, but also blocked the Akt phosphorylation after MCMV infection (P=0.031), however no significant influence was observed in control group. Conclusions MCMV induces phenotypic modulation of vascular smooth muscle, PI3K/Akt signaling pathway may be involved in the process of MCMV promoting the phenotype transformation of smooth muscle cells. Key words: Cytomegalovirus; Vascular smooth muscle cell; Phenotypic switching; PI3K/Akt